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M Prinz

Publications and source records attributed to M Prinz.

At least 19 recordsLinked to original sources
PubMed2001

DNA Commission of the International Society of Forensic Genetics: recommendations on forensic analysis using Y-chromosome STRs.

During the past few years, the DNA Commission of the International Society of Forensic Genetics has published a series of documents providing guidelines and recommendations concerning the application of DNA polymorphisms to the problems of human identification. This latest report addresses a relatively new area - namely, Y-chromosome polymorphisms, with particular emphasis on short tandem repeats (STRs). This report addresses nomenclature, use of allelic ladders, population genetics and reporting methods.

Alleles↗
PubMed2001

Further characterization and population data for the pentanucleotide STR polymorphism D10S2325.

Pentanucleotide tandem repeat markers are interesting for forensic sciences, because they may present less stutter on the electrophoretic pattern. We focused on the analysis of the DNA sequence for each allele at the pentanucleotide STR locus D10S2325 in order to understand their structures in the human genome and to construct human allelic ladder, which is necessary for forensic DNA typing. In order to evaluate the forensic applicability of D10S2325 and to construct a preliminary database, the genotype distributions and allele frequencies in three major ethnic groups were investigated. The population samples included Caucasians (Germans), Africans (African Americans), and Asians (Chinese). A total of 520 samples from unrelated individuals was analyzed by Amp-FLP. An example of each allele and new alleles were sequenced. Allele determination was carried out by comparison with a sequenced human allelic ladder made in-house. This pentanucleotide STR provided easily interpretable results. A total of 15 alleles was found in our population samples. Three new alleles were observed and named as alleles 19 and 21 based on the number of repeat motifs, while allele 19 can be divided further into two alleles, 19a and 19 according to analysis of the sequence. No evidence of deviation from Hardy-Weinberg equilibrium was observed. In 64 confirmed father/mother/child triplets no mutation event was observed. Using a maximum likelihood method, the mutation rate was indirectly estimated as 2.5 x 10(-5). These results suggest that D10S2325 is a useful marker for forensic casework and paternity analysis.

Black or African American↗
PubMed2001

Sequence structure of 12 novel Y chromosome microsatellites and PCR amplification strategies.

In this work, we present sequencing data for 12 recently reported Y STR loci (DYS434, DYS435, DYS436, DYS437, DYS438, DYS439, GATA A10, GATA 7.1, GATA 7.2, GATA C4, GATA H4, GATA A4), as well as the PCR multiplex strategies we implemented for their detection. Sequenced allelic ladders were constructed and a nomenclature for these new systems is proposed based on the sequence structure and following ISFG recommendations.GATA A4 and DYS439 are likely the same STR. They have the same STR structure and the alleles are always the same in the same individuals.Sequence polymorphisms were observed in the GATA C4 and DYS437 STRs. The variation in DYS437 was associated with a specific population group and is very interesting not only for forensic genetics but also for anthropological studies.

Alleles↗
PubMed2001

Validation and casework application of a Y chromosome specific STR multiplex.

A series of validation experiments was performed for a Y chromosome specific STR multiplex system following the suggestions made by the Technical Working Group DNA Analysis Methods (TWGDAM). The multiplex PCR products were detected on Perkin-Elmer 373 and 377 automated sequencers using two labeling colors. No problems regarding the stability, robustness and sensitivity of the Y STR multiplex were observed. Mixture studies revealed a cut off rate similar to autosomal STRs for mixtures of male DNAs and no interference of any female admixture. The comparison of the Y STR results to the autosomal typing results for 56 nonprobative semen stains and swabs, showed a slightly higher success rate in detecting the semen donor's alleles for the Y STR multiplex. Two examples are shown to illustrate the usefulness of Y STR typing for DNA mixtures. In one case the Y STR results confirmed an isolated exclusion; in the other case, the interpretation of a mixture was clarified since the Y STR results proved the presence of DNA from at least two semen donors. Y STR typing is a valuable addition to the forensic DNA testing panel.

Alleles↗
PubMed2001

Allele sequences of six new Y-STR loci and haplotypes in the Chinese Han population.

Human chromosome Y-specific short tandem repeat (Y-specific STR) markers have useful properties for forensic applications. However, there is a need to develop more Y-specific STR markers, because the discriminating power of each STR locus is limited. In the present study, we describe our results on six new Y-specific STR markers that were initially located using sequence database information by Ayub et al. and were named DYS434, DYS435, DYS436, DYS437, DYS438 and DYS439. Our studies focused on the analysis of the DNA sequence for each allele at all six Y-specific STR loci in order to understand their structures in the human genome and to construct human allelic ladders, which are necessary for forensic DNA typing. In addition, the haplotype distribution for all six analyzed loci was studied in a Chinese Han population sample. The results indicate that DYS434, DYS435, DYS436, DYS437, DYS438 and DYS439 are useful Y-specific STR markers for forensic sciences.

Alleles↗
PubMed2001

beta-adrenergic receptor stimulation selectively inhibits IL-12p40 release in microglia.

The cytokine interleukin-12 (IL-12) is mainly produced in response to bacterial or parasitic infections. We examined the capacity of mouse brain microglia to release IL-12 forms upon challenge with bacterial lipopolysaccharide (LPS) and studied its modulation by sympathomimetics. LPS evoked the release of IL-12p40 whereas the heterodimeric form, IL-12p70 was virtually undetectable. Sympathomimetics such as salbutamol dose-dependently inhibited IL-12p40 release, whereas the production of IL-6, TNFalpha and MIP-1alpha was only marginally influenced. The inhibitory effect of salbutamol could be abolished by beta-antagonists, such as oxprenolol. The cAMP-elevating agent forskolin could mimic the effects of beta-agonists, indicating that IL-12p40 release inhibition involves intracellular cAMP accumulation. While microglial IL-12p40 may play a role in the regulation of IL-12p70 bioactivity, microglial release is itself modulated by IL-12p70. Recombinant IL-12p70 was found to enhance the LPS-evoked release of MIP-1alpha and to have a biphasic effect on both TNFalpha and MIP-1alpha with release augmentation at lower and attenuation at higher doses. Finally, no functional correlation was found between the release of IL-12p40 and the induction of Kv1.3 potassium channels, another marker of microglial activation. Taken together, beta(2)-adrenoreceptor-mediated effects on microglial cyto- and chemokine release via cAMP accumulation could modulate inflammatory cascades during bacterial infections.

Adrenergic beta-Agonists↗
PubMed2001

The protein tyrosine kinase inhibitor AG126 prevents the massive microglial cytokine induction by pneumococcal cell walls.

Central nervous system (CNS) infections caused by Streptococcus pneumoniae still have a disastrous outcome. Underlying immunological and CNS cellular events are largely enigmatic. We used pneumococcal cells walls (PCW) to investigate microglial responses as these cells are prominent sensors and effectors during neuropathological changes. PCW stimulation of mouse microglia in vitro evoked the release of the cyto- and chemokines, TNF-alpha, IL-6, IL-12, KC, MCP-1, MIP-1alpha, MIP-2 and RANTES as well as soluble TNF receptor II, a potential TNF-alpha antagonist. The release induction followed extremely steep dose-response relations, and short exposure periods (15 min) were already sufficient to trigger substantial responses. PCW signaling controlling the release depended on both p38 and p42/p44 (ERK2/ERK1) MAP kinase activities. The kinase inhibitor, tyrphostin AG126 prevented the PCW-inducible phosphorylation of p42/p44(MAPK), potently blocked cytokine release and drastically reduced the bioavailable TNF-alpha, since it only marginally affected the release of soluble TNF receptors. Moreover, in an in vivo model of pneumococcal meningitis, AG126 significantly attenuated the PCW-induced leukocyte influx to the cerebrospinal fluid. The findings imply that pneumococcal CNS infection can cause a rapid and massive microglial activation and that ERK/MAPK pathway(s) are potential targets for pharmacological interventions.

Animals↗
PubMed2001

Human herpes virus-8 is not associated with primary central nervous system lymphoma in HIV-negative patients.

Primary central nervous system lymphomas (PCNSL) are derived from germinal center B cells. Recent molecular studies indicate that the tumor cells or their precursors have experienced antigenic stimulation. Attractive candidates for such antigens are pathogens with the capacity to reside in the brain. The aim of the present study was to evaluate whether human herpes virus (HHV)-8 is involved in the pathogenesis of PCNSL. A series of 46 PCNSL, 31 from HIV-negative and 15 from HIV-positive patients, were analyzed using various molecular biological and immunological approaches. Nested PCR with two different protocols unequivocally demonstrated that PCNSL from HIV-negative patients did not harbor HHV-8 DNA. Among AIDS-associated PCNSL, HHV-8 DNA was found in only 1 tumor. In situ hybridization studies revealed that the lymphoma cells were HHV-8 negative in all cases. Single small mononuclear cells, most likely corresponding to bystander lymphocytes, were identified as the cellular source of HHV-8 in the HIV-positive patient with an HHV-8 PCR signal. These studies largely rule out a role for HHV-8 in the pathogenesis of PCNSL in both HIV-negative as well as HIV-positive patients.

Adult↗
PubMed2001

DNA commission of the International Society of Forensic Genetics: recommendations on forensic analysis using Y-chromosome STRs.

During the past few years the DNA commission of the International Society of Forensic Genetics has published a series of documents providing guidelines and recommendations concerning the application of DNA polymorphisms to the problems of human identification. This latest report addresses a relatively new area, namely Y-chromosome polymorphisms, with particular emphasis on short tandem repeats (STRs). This report addresses nomenclature, use of allelic ladders, population genetics and reporting methods.

Alleles↗
PubMed2001

Interventional strategies against prion diseases.

Only a few years ago, the idea that transmissible spongiform encephalopathies could be treated pharmacologically would have met with considerable scepticism. Even now, there is no way to cure a patient or animal suffering from a manifest prion disease. But recent, exciting developments seem to indicate that immunological and pharmacological interventions could have some potential for the pre-exposure and post-exposure prophylaxis of prion diseases. Although it is unlikely that we will be able to cure the clinically overt stages of prion diseases in the foreseeable future, palliative and even life-prolonging interventions might no longer be confined to the realm of science fiction.

Animals↗
PubMed2001

Targeting gene-modified hematopoietic cells to the central nervous system: use of green fluorescent protein uncovers microglial engraftment.

Gene therapy in the central nervous system (CNS) is hindered by the presence of the blood-brain barrier, which restricts access of serum constituents and peripheral cells to the brain parenchyma. Expression of exogenously administered genes in the CNS has been achieved in vivo using highly invasive routes, or ex vivo relying on the direct implantation of genetically modified cells into the brain. Here we provide evidence for a novel, noninvasive approach for targeting potential therapeutic factors to the CNS. Genetically-modified hematopoietic cells enter the CNS and differentiate into microglia after bone-marrow transplantation. Up to a quarter of the regional microglial population is donor-derived by four months after transplantation. Microglial engraftment is enhanced by neuropathology, and gene-modified myeloid cells are specifically attracted to the sites of neuronal damage. Thus, microglia may serve as vehicles for gene delivery to the nervous system.

Animals↗
PubMed2001

Similar effects of atorvastatin, simvastatin and pravastatin on thrombogenic and inflammatory parameters in patients with hypercholesterolemia.

BACKGROUND: Previous studies have suggested that statins exert beneficial effects beyond their favorable lipid lowering effect. Particularly, the modification of thrombus formation and degradation, alteration in inflammatory response, plaque stabilization and improved endothelial function are thought to be responsible for additional reduction of morbidity and mortality due to cardiovascular events. To date, however, it is still unclear whether these effects are elicited by all statins. METHODS AND RESULTS: We set out to compare in a controlled, randomized, double-blind study design the effects of almost equieffective cholesterol lowering doses of three chemically and pharmacokinetically different statins (atorvastatin, simvastatin, pravastatin) on hemostatic and inflammatory markers in 99 hypercholesterolemic patients. At entry and 3 months after onset of statin therapy plasma cholesterol and von Willebrand factor antigen (vWf-Ag), fibrinogen, d-dimer, prothrombin fragment 1+2 (F1.2) and C-reactive protein (CRP) were measured. The effect on plasma values of F1.2, vWf-Ag, d-dimer and CRP was not significantly different between the three treatment groups. The effect of simvastatin on fibrinogen (p = 0.005) was more pronounced than the effects of atorvastatin (p = 0.48 n.s.) and pravastatin (p = 0.15 n.s.). Plasma levels of F1.2 and vWf-Ag (when data of all statins were pooled) were significantly reduced by 7% and 10% versus baseline, respectively. No significant reduction was observed for d-dimer (p = 0.26) and CRP (p = 0.5). Total plasma cholesterol levels decreased significantly (p < 0.0001 in all groups) between 22% and 29% compared to baseline. CONCLUSION: The present study shows similar short-term (3 months) effects of atorvastatin, simvastatin and pravastatin on selected hemostatic and inflammatory parameters in plasma in patients with hypercholesterolemia. Thus, chemical and pharmacological differences between statins appear to exert no major influence on these parameters.

Adult↗
PubMed2001

Y chromosome-specific short tandem repeats in forensic casework.

Several case examples are presented to illustrate the usefulness of Y chromosome specific human DNA markers in a forensic setting. The markers used are the tetrameric short tandem repeats (STR's) DYS19, DYS389I, DYS389II, and DYS390. The main advantage of the Y-STR approach is the ability to detect the male component in a mixture of male and female DNA. It is also useful for the determination of the number of semen donors for mixtures of two or more male individuals.

DNA Fingerprinting↗
PubMed2000

Mice trisomic for a bacterial artificial chromosome with the single-minded 2 gene (Sim2) show phenotypes similar to some of those present in the partial trisomy 16 mouse models of Down syndrome.

The Drosophila single-minded (sim) transcription factor, is a master regulator of fruitfly neurogenesis. Recently, we have cloned and mapped a human homolog of sim, SIM2, to chromosome 21 in the so-called 'Down syndrome chromosomal region'. Three copies of SIM2 may contribute to some Down syndrome (DS) phenotypes because of the mapping position function as transcriptional repressor, temporal and spatial expression pattern of mouse Sim2, and the potentially analogous role of human SIM2 to that of Drosophila sim during neurogenesis. In order to validate this hypothesis in vivo, we have created the first bacterial artificial chromosome transgenic mice overexpressing a gene possibly involved in DS with only one or two additional copies of mouse Sim2. The transgene was shown to be expressed in the same spatial pattern as the endogenous gene. The mice develop normally, are fertile and do not show detectable histopathological abnormalities. However, detailed analysis of their behavior revealed anxiety-related/reduced exploratory behaviour and sensitivity to pain, phenotypes similar to those also present in other partial trisomy 16 mouse models of DS. Our data therefore suggest that overexpression of SIM2 contributes to some of the complex DS phenotypes.

Animals↗
PubMed2000

Voltage- and gamma-aminobutyric acid-activated membrane currents in the human medulloblastoma cell line MHH-MED-3.

The whole-cell patch clamp technique was used to characterize voltage- and neurotransmitter-activated currents in the medulloblastoma cell line MHH-MED-3 and cells from tissue slices and primary cultures of two medulloblastoma biopsies. These preparations revealed similar electrophysiological properties. All tested cells displayed 4-aminopyridine-sensitive delayed rectifying K(+) currents, gamma-aminobutyric acid(A) receptor-mediated Cl(-) currents and most of them inward rectifier K(+) currents. Transient inward currents were mainly carried by low-voltage activated T-type Ca(2+) channels in MHH-MED-3 cells, and tetrodotoxin-sensitive Na(+) channels in cells from the primary culture. From these characteristics we conclude that medulloblastoma cells share physiological features with developing cerebellar granule cells at an immature stage.

Adolescent↗